Riklund K E, Makiya R A, Sundström B E, Thornell L E, Stigbrand T I
Department of Physiological Chemistry, University of Umeå, Sweden.
Anticancer Res. 1990 Mar-Apr;10(2A):379-84.
The radioimmunotherapeutic potential of 131I-labeled monoclonal antibodies was investigated in 36 nude mice (BALB/c nu/nu) inoculated s.c. with the HeLa Hep 2 human adenocarcinoma cell line. The membrane bound tumour associated antigen placental alkaline phosphatase and several intracellular cytokeratins served as targets for the antibodies. The specific radioactivity in each organ was determined after i.p. injection of the 131I-labeled antibodies (0.2-0.3 mg, approximately 15 MBq/animal), and high localization to the tumours was seen. Significant growth inhibition was observed after injection of the radiolabeled monoclonal antibody H7 against the placental alkaline phosphatase, which reduced the tumour growth to only 12% during a 3 week period compared to a growth of more than 100% for the controls. Animal weight losses were seen. Synthesis of endogenous antibodies to the target antigens was found to be significant. Morphometric evaluation of the relations between stroma, tumour cells and necrotic areas in the tumours after radioimmunotherapy demonstrated a significant increase of the mean relative connective tissue volume and a significant decreased mean of relative volume of tumour cells in the group treated with iodinated antiplacental alkaline phosphatase antibody. This therapeutic principle is encouraging and may offer new possibilities for future treatment of some malignant diseases.
在36只皮下接种人宫颈癌HeLa Hep 2细胞系的裸鼠（BALB/c nu/nu）中研究了¹³¹I标记单克隆抗体的放射免疫治疗潜力。膜结合肿瘤相关抗原胎盘碱性磷酸酶和几种细胞内角蛋白作为抗体的靶点。经腹腔注射¹³¹I标记抗体（0.2 - 0.3 mg，约15 MBq/只动物）后，测定各器官的比放射性，可见肿瘤部位有高度聚集。注射针对胎盘碱性磷酸酶的放射性标记单克隆抗体H7后观察到显著的生长抑制，与对照组超过100%的生长相比，在3周内肿瘤生长仅为12%。观察到动物体重减轻。发现针对靶抗原的内源性抗体合成显著。放射免疫治疗后对肿瘤中基质、肿瘤细胞和坏死区域之间关系的形态计量学评估显示，用碘化抗胎盘碱性磷酸酶抗体治疗的组中，平均相对结缔组织体积显著增加，肿瘤细胞相对体积平均值显著降低。这一治疗原理令人鼓舞，可能为未来某些恶性疾病的治疗提供新的可能性。
